Pazopanib Hydrochloride, Paclitaxel, and Carboplatin in Treating Patients With Refractory or Resistant Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

NCT01402271 | Completed Phase 1

• 3 other identifiers: EORTC-55092EU-211192010-024077-39
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 9

Brief Summary

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of pazopanib hydrochloride when given together with paclitaxel and carboplatin in treating patients with refractory or resistant ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer.

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer; recurrent fallopian tube cancer; recurrent primary peritoneal cavity cancer

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose of pazopanib hydrochloride, carboplatin, and paclitaxel (phase I)

• Progression-free survival according to RECIST 1.1 at 1 year (phase II)

Secondary Outcomes (6)

• Pharmacokinetics of pazopanib, carboplatin, and paclitaxel (phase I)

• Safety and tolerability according to CTCAE 4.0 (phase I and phase II)

• Response rate (phase I and phase II)

• Predictive biomarkers (phase I and phase II)

• Overall survival (phase II)

Study Arms (2)

pazopanib in combination with paclitaxel and carboplatin

EXPERIMENTAL

Phase I: Dose-escalation study of pazopanib in combination with paclitaxel and carboplatin given weekly in a group of patients with platinum-refractory or -resistant ovarian, fallopian tube or peritoneal carcinoma Phase II: Paclitaxel 30 mg/m² and Carboplatin 2.0 AUC weekly for 18 courses PLUS Pazopanib 400 mg daily

Drug: carboplatin; Drug: paclitaxel; Drug: pazopanib hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

Paclitaxel and carboplatin only

ACTIVE COMPARATOR

Carboplatin AUC 2.7 and paclitaxel 60mg/m² weekly for 18 courses.

Drug: carboplatin; Drug: paclitaxel; Drug: pazopanib hydrochloride

Interventions

carboplatin DRUG

Paclitaxel and carboplatin only; pazopanib in combination with paclitaxel and carboplatin

paclitaxel DRUG

Paclitaxel and carboplatin only; pazopanib in combination with paclitaxel and carboplatin

pazopanib hydrochloride DRUG

Paclitaxel and carboplatin only; pazopanib in combination with paclitaxel and carboplatin

laboratory biomarker analysis OTHER

pazopanib in combination with paclitaxel and carboplatin

pharmacological study OTHER

pazopanib in combination with paclitaxel and carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial, fallopian tube, or peritoneal carcinoma * Recurrent disease * Received at least 1 prior platinum treatment and developed platinum-refractory disease (i.e., progression within 4 weeks of platinum administration) or platinum-resistant disease (i.e., progression within 6 months after the last platinum dose) * There is no restriction on the number of prior lines of treatment * Non-platinum treatment is allowed after proven platinum-resistance or -refractory disease * Evaluable (measurable or nonmeasurable) disease according to RECIST version 1.1 criteria * Patients with refractory disease on weekly paclitaxel and carboplatin regimen are excluded (phase II only) * No known gastrointestinal intraluminal metastatic lesions with risk of bleeding * No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels * No known brain metastases or leptomeningeal disease PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100 x 10\^9/L * PT, aPTT, or INR ≤ 1.2 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN\* * ALT and AST ≤ 2.5 times ULN\* * Serum creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min * Urine protein creatinine ratio \< 1 OR 24-hour urine protein \< 1 g * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during study therapy * No other prior primary or recurrent malignancies treated within the past 2 years except for completely resected non-melanomatous skin carcinoma or successfully treated carcinoma in situ of the skin or uterine cervix * No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs similar or related to paclitaxel, carboplatin, and pazopanib hydrochloride * Able to receive infusions of paclitaxel and carboplatin * Able to swallow pazopanib hydrochloride tablets * No unstable or serious condition (e.g., uncontrolled infection requiring systemic therapy) * No history of any of the following cardiovascular conditions within the past 6 months: * Myocardial infarction * Unstable angina * Symptomatic peripheral vascular disease * NYHA class III-IV congestive heart failure * LVEF \> 50% as assessed by ultrasound or MUGA scan, if clinically indicated * No inadequately controlled hypertension (SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg) * Initiation or adjustment of blood pressure medication is permitted prior to the study entry * No prolonged corrected QT interval (QTc) defined as \> 480 msecs using Bazett formula * No history of cerebrovascular accident within the past 6 months, including any of the following: * Transient ischemic attack * Pulmonary embolism * Untreated deep venous thrombosis (DVT) * Patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible * No evidence of active bleeding or bleeding diathesis * No clinically significant gastrointestinal (GI) tract abnormalities that may increase the risk for GI bleeding including, but not limited to, any of the following: * Active peptic ulcer disease * Inflammatory bowel disease (e.g., ulcerative colitis or Crohn disease) * No history of bowel obstruction (excluding postoperative (i.e. within 4 weeks post surgery)) during the whole prior history of the patient, or other GI condition with increased risk of perforation such as clear infiltration into the rectosigmoid, colon or small bowel. * No clinically significant GI abnormalities that may affect absorption of investigational product including, but not limited to, any of the following: * Malabsorption syndrome * Major resection of stomach or small bowel * No hemoptysis in excess of 2.5 mL (one-half teaspoon) within 8 weeks prior to first dose of study drug * No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * No trauma within the past 28 days * No prior non-healing wounds, fracture, or ulcer PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No ongoing toxicity from prior anticancer therapy \> grade 1 and/or that is progressing in severity, except for alopecia and ≤ grade 2 peripheral neuropathy * No cardiac angioplasty or stenting within the past 6 months * No coronary artery bypass graft surgery within the past 6 months * At least 14 days since prior radiotherapy, surgery, or tumor embolization , chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy (28 days for drugs with a longer half-life) * At least 14 days since prior (28 days for drugs with a longer half-life) and no concurrent prohibited medications * At least 28 days since prior major surgery (procedures such as catheter placement and diagnostic endoscopic procedures are not considered to be major)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (9)

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, Belgium

Location

U.Z. Gasthuisberg

Leuven, Belgium

Location

C.H.U. Sart-Tilman

Liège, Belgium

Location

Centre Hospitalier Regional De La Citadelle

Liège, Belgium

Location

ZNA Jan Palfijn

Merksem, Belgium

Location

Radboud University Medical Center Nijmegen

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Badalona, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, Spain

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2011
• First Posted: July 26, 2011
• Study Start: July 1, 2012
• Primary Completion: May 15, 2019
• Study Completion: July 13, 2020
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

BE (5); NL (2); ES (2)